Objectives Currently there is a paucity of clinically available regenerative therapies for stroke. Extracellular vesicles (EV) have been investigated for their potential as modulators of regeneration in the poststroke brain. This systematic review and meta-analysis aims to provide a summary of the efficacy of therapeutic EVs in preclinical stroke models, to inform future research in this emerging field.
Methods Studies were identified by a comprehensive literature search of two online sources and subsequent screening. Studies using lesion volume or neurological score as outcome measures were included. Standardised mean difference (SMD) and 95% CIs were calculated using a restricted maximum likelihood random effects model. Publication bias was assessed with Egger’s regression and presented as funnel plots with trim and fill analysis. Subgroup analysis was performed to assess the effects of different study variables. Study quality and risk of bias were assessed using the CAMARADES checklist.
Results A total of 20 publications were included in the systematic review, of which 19 were assessed in the meta-analysis (43 comparisons). Overall, EV interventions improved lesion volume (SMD: −1.95, 95% CI −2.72 to 1.18) and neurological scores (SMD: −1.26, 95% CI −1.64 to 0.87) compared with control groups. Funnel plots were asymmetrical suggesting publication bias, and trim and fill analysis predicted seven missing studies for lesion volume. Subgroup analysis suggested administration at 0–23 hours after stroke was the most effective timepoint for EV treatment. The median score on the CAMARADES checklist was 7 (IQR: 5–8).
Conclusions EVs may offer a promising new avenue for stroke therapies, as EV-based interventions had positive impacts on lesion volume and neurological score in preclinical stroke models.
PROSPERO registration number CRD42019134925.
- extracellular vesicles
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JMT and CJC contributed equally.
Contributors JMT, CJC and SMA conceived and designed the study. JMT and CJC performed the systematic review, with input from SMA, and wrote the manuscript. CBL and EP provided input to the study design and commented on draft manuscript. JMT and CJC contributed equally.
Funding This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) Doctoral Prize Fellowship grant EP/N509565/1 and EPSRC and Medical Research Council (MRC) Centre for Doctoral Training in Regenerative Medicine studentship grant EP/L014904/1.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available in a public, open access repository. Access: https://doi.org/10.5281/zenodo.3580718
Open data https://doi.org/10.5281/zenodo.3580718
Preregistration The systematic review and meta-analysis reported in this article was formally preregistered on PROSPERO (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019134925). The data and the data analysis scripts are available at https://doi.org/10.5281/zenodo.3508718. The materials used are widely available
Open peer review Prepublication and Review History is available online at http://dx.doi.org/10.1136/bmjos-2019-100047.
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